Neisseria meningitidis, also called meningococcus, is a bacterium responsible for meningitis and septicemia. Its most serious form, purpura fulminans, is often fatal. This bacterium, which is naturally present in humans in the nasopharynx, is pathogenic if it reaches the blood stream. Teams led by Dr. Sandrine Bourdoulous, CNRS senior researcher at the Institut Cochin, have deciphered the molecular events through which meningococci target blood vessels and colonize them. This work opens a path to new therapeutic perspectives for treating vascular problems caused by this type of invasive infection. The study was published on June 1, 2014 in Nature Medicine.

When the bacterium Neisseria meningitidis multiplies in the blood, it interacts with the endothelial cells that line the inside of blood vessels and adheres to their walls. In the skin and mucous membranes, meningococcal infection in the vessels creates hemorrhagic skin lesions (called purpura) due to bleeding in the tissues. Those can rapidly progress to a serious and often fatal form of the disease (purpura fulminans). In the brain, when meningococci adhere to the vessels they can pass through the blood-brain barrier, and cause meningitis when they invade the meninges.

Teams of researchers have deciphered how Neisseria meningitidis adheres to blood vessels, a step that underpins the bacterium's pathogenicity. In blood vessels they have identified receptor CD147, whose expression is essential for initial meningococcal adherence to endothelial cells. If this receptor is absent, N. meningitidis cannot implant in blood vessels and colonize them.

It is a well-known fact that the adherence process of meningococcal bacteria to human cells relies on pili, long filaments that are expressed by the bacterium and composed of different sub-units (pilins). However, the pilins specifically involved in N. meningitidis' adherence to blood vessels had never been identified. The researchers have determined that two pilins, PilE and PilV, interact directly with the CD147 receptor. Without them, meningococci cannot adhere to endothelial cells.

Humans are the only species that can be infected by meningococci. To show in vivo that pilins PilE and PilV are essential for N. meningitidis to colonize the vascular network, the researchers used a mouse model, where the mice were immunodeficient and grafted with human skin, keeping the functional human vessels within the graft to reproduce in mice the infection stages as observed in human skin. These mice were then infected by meningococci naturally having pilins PilE and PilV, or meningococci in which the expression of these pilins had been artificially suppressed. The human blood vessels were only infected by meningococci displaying PilE and PilV, which confirms that these two pilins are essential to the bacterial colonization process.

The researchers also showed in an ex vivo infection model that cerebral vessels and meninges, particularly rich in CD147 receptors, allow colonization by meningococci, unlike other parts of the brain.

The scientists now wish to develop a new type of vaccine (to complement those already available) that would block the interaction between N. meningitidis and the CD147 receptors, thereby stopping the bacterium from colonizing the vessels.

Related Stories

Researchers at the Paris Cardiovascular Research Center (PARCC) have shown how adhesion of Neisseria (N.) meningitidis to human microvessels in a humanized mouse model leads to the characteristic cutaneous lesions of meningococcal ...

When tumours grow, new blood vessels are formed that deliver oxygen and nutrients to the tumour cells. A research group at Uppsala University has discovered a new type of cell communication that results in suppressed blood ...

(Medical Xpress)—Leukaemia drugs could help to improve treatments for blindness caused by abnormal blood vessel growth in the eye, finds new UCL research. The study, published in the Journal of Experimental Medicine, raises ...

By discovering a new mechanism that allows blood to enter the brain immediately after a stroke, researchers at UC Irvine and the Salk Institute have opened the door to new therapies that may limit or prevent stroke-induced ...

Recommended for you

Short telomeres—the protective caps on the ends of chromosomes—have been previously linked to increased risk of death from heart disease. Now, research by scientists at UC San Francisco and the Veterans Affairs Medical ...

Researchers led by ETH Professor Martin Fussenegger at the Department of Biosystems Science and Engineering (D-BSSE) in Basel have produced artificial beta cells using a straightforward engineering approach.

Medical students are taught that once infected with Toxoplasma gondii—the "cat parasite"—then you're protected from reinfection for the rest of your life. This dogma should be questioned, argue researchers in an Opinion ...

A team of scientists has uncovered details of the cellular mechanisms that control the direct programming of stem cells into motor neurons. The scientists analyzed changes that occur in the cells over the course of the reprogramming ...

Loss of a key protein leads to defects in skeletal development including reduced bone density and a shortening of the fingers and toes—a condition known as brachydactyly. The discovery was made by researchers at Penn State ...

Researchers from the University of Pittsburgh School of Medicine and UPMC have engineered a protein that reverses carbon monoxide (CO) poisoning in mice, a discovery that could potentially lead to the creation of the first ...

0 comments

Please sign in to add a comment.
Registration is free, and takes less than a minute.
Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.